1. Field of the Invention
The present invention relates generally to the field of biomedical engineering. More specifically, the present invention relates to a novel reactor for making uniform capsules.
2. Description of the Related Art
Capsules, with semipermeable polymer membranes as their walls, have been employed as the media for a variety of medical applications, such as controlled release of medicines and immunoisolation of hormone-producing cells, such as pancreatic islets, etc. Polymer membrane design and the selection of the capsule inner liquid is being researched continuously.
The methodology of conventional capsule production involves the interaction of two reacting (oppositely charged) polymers, a drop of one in a bath of the other, leading to polyelectrolyte complex (membrane) formation. The reaction is turned off by quenching the capsule in a buffer after the appropriate reaction time (once an appropriate thickness of membrane has formed). The concentrations of the polymers influence the membrane qualities and permeability. The strength of the capsule and its immunoisolation efficiency is a function of its thickness, which depends on reaction time. Physically, the membrane functions as a flow regulator or molecular sieve, allowing passage of some molecules or retention of others, based on the size of the molecule.
An example of this methodology is as follows: assume that anion drops react with a cation bath to form capsules. If desired, the anion drops carry the encapsulant. A steady stream of anion drops can be produced by a variety of techniques. When anion viscosities are low (&lt;50 cS), capillary wave excitation on the anion jet and subsequent development of instability of the jet leads to precisely partitioned anion drops. However, when anion viscosities are higher, and especially while dealing with polymers, the more flexible route to drop production is through air stripping (see FIG. 1), wherein uniformly-sized drops are produced. In air stripping, individual drops are sheared off the nozzle by the air stream, and in principle, there is no restriction imposed on the rate of pumping of the anion (no need to pump a jet) and a rate of anion delivery can b e selected to suit the encapsulation needs. The only draw back to air stripping is that the drop pointing accuracy is not perfect and, depending on the anion viscosity, the trajectories of the stripped drops encompass a small cone angle.
One current goal is to make uniform capsules from anion drops of uniform size, produced at a controlled rate. A conventional approach is to collect the anion drops in a bath of cation in a beaker. The problem with this approach is that when reaction rates are fast, such that the times for collection and reaction are very comparable, then the resulting capsules have varying wall thicknesses. For example, if the batch collection time is 30 seconds and the selected reaction time is 30 seconds, then the first capsule would have reacted for 60 seconds, whereas the last capsule would have reacted for only 30 seconds. Furthermore, since the cation in the beaker is continuously depleted by the reacting anion drops, the concentration of the cation is different between the first capsule and the last. This leads to heterogeneity in wall thickness, and membrane properties, between capsules (FIG. 2). Therefore, to minimize variability, one would have to keep the collection time much smaller than the reaction time. This can be problematic, if a large volume production is desired, whether in a laboratory or industrial setting. Another way to minimize variability is to slow down the anion-cation reaction rates, by diluting the concentrations of either, or both, or by other chemical means. Dilution, however, is not always possible without losing desired properties of the polymers. Also, with the conventional approach, when there is a substantial density mismatch between the anion drop and the cation solution, the capsule walls do not form uniformly around the drop. This is because during processing, the capsules will either settle at the bottom of the beaker or collect at the top interface. Stirring does not always solve this problem.
The goal for capsule production is now well defined; viz., to design an apparatus that can continuously generate capsules at a high rate, with precise control of reaction time, and with uniform exposure of the developing capsule to the cation. Clearly, it is preferable that such an apparatus would require very little attention during operation. Additionally, the economy of cation usage merits consideration, for the cation can be expensive and neutralizing large volumes of cation with buffer to stop the reaction is very cumbersome.
The prior art is deficient in the lack of an effective capsule producing apparatus that continuously can generate uniform capsules at a high rate of production with very little monitoring. The present invention fulfills this longstanding need and desire in the art.